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A Three-Dimensional Computer Model of Four Hypothetical Mechanisms Protecting Biofilms from Antimicrobials

Chambless, Jason D., Hunt, Stephen M., Stewart, Philip S.
Applied and environmental microbiology 2006 v.72 no.3 pp. 2005-2013
computers, growth and development, experimental design, biofilm, growth models, anti-infective agents
Four hypothetical mechanisms for protection of biofilms against antimicrobials were incorporated into a three-dimensional model of biofilm growth and development. The model integrated processes of substrate utilization, diffusion, growth, cell migration, death, and detachment in a cellular automaton framework. Compared to simulations of unprotected biofilms, each of the protective mechanisms provided some tolerance to antimicrobial action. When the mechanisms were compared to each other, the behaviors of the four protective mechanisms produced distinct shapes of killing curves, nonuniform spatial patterns of survival and cell type distribution, and anticipated susceptibility patterns for dispersed biofilm cells. The differences between the protective mechanisms predicted in these simulations could guide the design of experiments to discriminate antimicrobial tolerance mechanisms in biofilms. Each of the mechanisms could be a plausible avenue of biofilm protection.